Smac mimetics and innate immune stimuli synergize to promote tumor death.

Smac mimetic compounds (SMC), a class of drugs that sensitize cells to apoptosis by counteracting the activity of inhibitor of apoptosis (IAP) proteins, have proven safe in phase 1 clinical trials in cancer patients. However, because SMCs act by enabling transduction of pro-apoptotic signals, SMC monotherapy may be efficacious only in the subset of patients whose tumors produce large quantities of death-inducing proteins such as inflammatory cytokines. Therefore, we reasoned that SMCs would synergize with agents that stimulate a potent yet safe "cytokine storm.

Efficient generation of functional transgenes by homologous recombination in murine zygotes.

To assess the feasibility of generating functional transgenes directly via homologous recombination between microinjected DNA fragments, three overlapping genomic DNA fragments, together constituting the human serum albumin (hSA) gene, were coinjected into murine zygotes. The resulting transgenic mice were analyzed for structure and expression of the transgene. All transgenic mice carried recombined hSA DNA fragments and 74% contained a reconstituted hSA gene.